Method and apparatus for predicting acute response to cardiac resynchronization therapy at a given stimulation site

ABSTRACT

Response to cardiac resynchronization therapy is predicted for a given stimulation site so that an atrioventricular delay of an implantable device administering cardiac resynchronization therapy may be set to a proper amount. The first deflection of ventricular depolarization is measured, such as through a surface electrocardiogram or through an intracardiac electrogram measured by a lead positioned in the heart at the stimulation site. The maximum deflection of the ventricular depolarization is then measured by the lead positioned at the stimulation site. The interval of time between the first deflection and the maximum deflection of the ventricular depolarization is compared to a threshold to determine whether the stimulation site is a responder site. If the interval is larger than the threshold, then the site is a responder and the atrioventricular delay of the implantable device may be set to less than the intrinsic atrioventricular delay of the patient. Otherwise, the atrioventricular may be set to approximately equal the intrinsic atrioventricular delay.

TECHNICAL FIELD

[0001] The present invention relates generally to a method and apparatusfor administering stimulation therapy for heart disease and, moreparticularly, to a method and apparatus for predicting acute response tocardiac resynchronization therapy for a given stimulation site.

BACKGROUND

[0002] The heart is a muscular organ comprising multiple chambers thatoperate in concert to circulate blood throughout the body's circulatorysystem. As shown in FIG. 1, the heart 100 includes a right-side portionor pump 102 and a left-side portion or pump 104. The right-side portion102 includes a right atrium 106 and a right ventricle 108. Similarly,the left-side portion 104 includes a left atrium 110 and a leftventricle 112. Oxygen-depleted blood returning to the heart 100 from thebody collects in the right atrium 106. When the right atrium 106 fills,the oxygen-depleted blood passes into the right ventricle 108 where itcan be pumped to the lungs (not shown) via the pulmonary arteries 117.Within the lungs, waste products (e.g., carbon dioxide) are removed fromthe blood and expelled from the body and oxygen is transferred to theblood. Oxygen-rich blood returning to the heart 100 from the lungs viathe pulmonary veins (not shown) collects in the left atrium 110. Thecircuit between the right-side portion 102, the lungs, and the leftatrium 110 is generally referred to as the pulmonary circulation. Whenthe left atrium 110 fills, the oxygen-rich blood passes into the leftventricle 112 where it can be pumped throughout the entire body. In sodoing, the heart 100 is able to supply oxygen to the body and facilitatethe removal of waste products from the body.

[0003] To circulate blood throughout the body's circulatory system asdescribed above, a beating heart performs a cardiac cycle that includesa systolic phase and a diastolic phase. During the systolic phase (e.g.,systole), the ventricular muscle cells of the right and left ventricles108, 112 contract to pump blood through the pulmonary circulation andthroughout the body, respectively. Conversely, during the diastolicphase (e.g., diastole), the ventricular muscle cells of the right andleft ventricles 108, 112 relax, during which the right and left atriums106, 110 contract to force blood into the right and left ventricles 108,112, respectively. Typically, the cardiac cycle occurs at a frequencybetween 60 and 100 cycles per minute and can vary depending on physicalexertion and/or emotional stimuli, such as, pain or anger.

[0004] The contractions of the muscular walls of each chamber of theheart 100 are controlled by a complex conduction system that propagateselectrical signals to the heart muscle tissue to effectuate the atrialand ventricular contractions necessary to circulate the blood. As shownin FIG. 2, the complex conduction system includes an atrial node 120(e.g., the sinoatrial node) and a ventricular node 122 (e.g., theatrioventricular node). The sinoatrial node 120 initiates an electricalimpulse that spreads through the muscle tissues of the right and leftatriums 106, 110 and the atrioventricular node 122. As a result, theright and left atriums 106, 110 contract to pump blood into the rightand left ventricles 108, 112 as discussed above. At the atrioventricularnode 122, the electrical signal is momentarily delayed beforepropagating through the right and left ventricles 108, 112. Within theright and left ventricles 108, 112, the conduction system includes rightand left bundle branches 126, 128 that extend from the atrioventricularnode 122 via the Bundle of His 124. The electrical impulse spreadsthrough the muscle tissues of the right and left ventricles 108, 112 viathe right and left bundle branches 126, 128, respectively. As a result,the right and left ventricles 108, 112 contract to pump blood throughoutthe body as discussed above.

[0005] Normally, the muscular walls of each chamber of the heart 100contract synchronously in a precise sequence to efficiently circulatethe blood as described above. In particular, both the right and leftatriums 106, 1 10 contract (e.g., atrial contractions) and relaxsynchronously. Shortly after the atrial contractions, both the right andleft ventricles 108, 112 contract (e.g., ventricular contractions) andrelax synchronously. Several disorders or arrhythmias of the heart canprevent the heart from operating normally, such as, blockage of theconduction system, heart disease (e.g., coronary artery disease),abnormal heart valve function, or heart failure.

[0006] Blockage in the conduction system can cause a slight or severedelay in the electrical impulses propagating through theatrioventricular node 122, causing inadequate ventricular relations andfilling. In situations where the blockage in the ventricles (e.g., theright and left bundle branches 126, 128), the right and/or leftventricles 108, 112 can only be excited through slow muscle tissueconduction. As a result, the muscular walls of the affected ventricle(108 and/or 112) do not contract synchronously (e.g., asynchronouscontraction), thereby, reducing the overall effectiveness of the heart100 to pump oxygen-rich blood throughout the body. For example,asynchronous contraction of the left ventricular muscles can degrade theglobal contractility (e.g., the pumping power) of the left ventricle 112which can be measured by the peak ventricular pressure change duringsystole (denoted as “LV+dp/dt”). A decrease in LV+dp/dt corresponds to aworsened pumping efficiency.

[0007] Similarly, heart valve disorders (e.g., valve regurgitation orvalve stenosis) can interfere with the heart's 100 ability to pumpblood, thereby, reducing stroke volume (i.e., aortic pulse pressure)and/or cardiac output.

[0008] Various medical procedures have been developed to address theseand other heart disorders. In particular, cardiac resynchronizationtherapy (“CRT”) can be used to improve the conduction pattern andsequence of the heart. CRT involves the use of an artificial electricalstimulator that is surgically implanted within the patient's body. Leadsfrom the stimulator can be affixed at a desired location within theheart to effectuate synchronous atrial and/or ventricular contractions.Typically, the location of the leads (e.g., stimulation site) isselected based upon the severity and/or location of the blockage.Electrical stimulation signals can be delivered to resynchronize theheart, thereby, improving cardiac performance.

[0009] Despite these advantages, several shortcomings exist that limitthe usefulness of CRT. For example, results from many clinical studieshave shown that hemodynamic response to CRT typically varies frompatient to patient, ranging from very positive (e.g., improvement) tosubstantially negative (e.g., deterioration). Additionally, hemodynamicresponse can also vary based upon the stimulation site used to applyCRT. Thus, in order to predict acute hemodynamic benefit from CRT, thepatient typically must be screened prior to receiving the therapy andthe actual stimulation site used to apply CRT should be validated foreach patient. Existing methods that predict acute hemodynamic responseto CRT are, therefore, patient specific. Furthermore, while someexisting techniques and/or procedures can predict whether a specificpatient will derive an acute hemodynamic benefit from CRT, they areunable to determine or validate that a specific stimulation site willproduce a positive hemodynamic response from CRT.

SUMMARY

[0010] Embodiments of the present invention provide methods and systemsthat detect whether a given stimulation site is a responder to CRT. Themethods and systems involve making measurements with at least oneelectrode implanted within the patient's heart. An implanted heartstimulation device, external device programmer, or other device may thendetermine from the measurements whether the stimulation site is aresponder site. An atrioventricular delay to be provided by thestimulation device to provide CRT to the patient can then be set to anappropriate amount based on the status of the stimulation site as aresponder or non-responder.

[0011] Acute response to cardiac resynchronization therapy may bepredicted for a given stimulation site of a patient by inserting a leadto the heart of the patient such that an electrode of the lead ispositioned at the stimulation site. A first deflection of an intrinsicventricular depolarization is then detected, followed by detection of amaximum deflection of the intrinsic ventricular depolarization at theelectrode. An interval of time between the first deflection and themaximum deflection is compared to a threshold to determine whether thestimulation site is a responder site.

[0012] One system for predicting acute response to cardiacresynchronization therapy at a stimulation site of a patient includes alead having an electrode placed at the stimulation site that detects anintrinsic ventricular depolarization. A surface electrocardiographmachine also detects the intrinsic ventricular depolarization. Aprocessing device finds an interval of time between a first deflectionof the intrinsic ventricular depolarization as detected by the surfaceelectrocardiograph machine and a maximum deflection of the intrinsicventricular depolarization as detected by the electrode of the lead. Theprocessing device compares the interval to a threshold to determinewhether the stimulation site is a responder.

[0013] Another system for predicting acute response to cardiacresynchronization therapy at a stimulation site of a patient includes alead having an electrode placed at the stimulation site that detects anintrinsic ventricular depolarization. A processing device finds aninterval of time between the first deflection and the maximum deflectionof the intrinsic ventricular depolarization as detected by the electrodeand compares the interval to a threshold to determine whether thestimulation site is a responder.

DESCRIPTION OF THE DRAWINGS

[0014]FIG. 1 is a diagram showing the various chambers of the heart.

[0015]FIG. 2 is a diagram showing the various chambers and theelectrical conduction system of the heart.

[0016]FIG. 3 is a graph showing ventricular depolarization as a functionof time and relating the ventricular depolarization as measured by asurface electrocardiograph and as measured by an intracardiacelectrogram.

[0017] FIGS. 4-6 are diagrams illustrating a heart and the electricalconduction system advancing through a normal cardiac cycle.

[0018]FIG. 7 is a graph illustrating mean percentage change in leftventricular pressure (LV+dp/dt) resulting from application of CRTplotted against the interval of first deflection to maximum deflectionof intrinsic ventricular depolarization for responder and non-respondersites.

[0019]FIG. 8 illustrates one possible embodiment of a system that can beused to detect whether a stimulation site is a responder to CRT byutilizing a surface electrocardiogram to detect the onset of ventriculardepolarization.

[0020]FIG. 9 illustrates another possible embodiment of a system thatcan be used to detect whether a stimulation site is a responder to CRTby utilizing intracardiac sensing to detect the onset of ventriculardepolarization.

[0021]FIG. 10 is an operational flow summarizing the logical operationsemployed by an exemplary system for detecting whether a patient is aresponder to CRT.

DETAILED DESCRIPTION

[0022] Various embodiments of the present invention will be described indetail with reference to the drawings, wherein like reference numeralsrepresent like parts and assemblies throughout the several views.Reference to various embodiments does not limit the scope of the presentinvention, which is limited only by the scope of the claims attachedhereto.

[0023] The following discussion is intended to provide a brief, generaldescription of a suitable method for predicting whether a stimulationsite is a positive responder to cardiac resynchronization therapy(“CRT”). As will be described in greater detail below, the method of thepresent disclosure predicts a stimulation site's response to CRT bymeasuring an interval that starts from a first deflection thatrepresents the far field reflexion of the ventricular activationsomewhere in the ventricles. The interval continues to a maximumdeflection of the same intrinsic ventricular depolarization thatrepresents the near field reflexion of the local activation of thetissue near an electrode, detected at the stimulation site where theresponse to CRT is being evaluated. The interval is then comparedagainst a threshold, and if the interval is larger than the thresholdthe site is defined as a positive responder to CRT. If the interval isnot larger than the threshold, then the site is defined as anon-responder site.

[0024] As will become apparent from the discussion below in connectionwith the various drawings, the first deflection of ventriculardepolarization may be measured in several different ways. For example,an onset of the depolarization may be found through processing of anintracardiac electrogram signal in the window that occurs before thebeginning of the large peak that corresponds to the near fieldventricular activation for that electrode. As another example, the onsetmay be found by processing of a signal measured by at least one surfaceelectrode to detect the beginning of the integrated far field activationsuch as through an ensemble averaging technique similar to thatdescribed in U.S. Pat. No. 5,235,976, which may also be applied whereintracardiac electrograms are used to find the onset. However, those ofordinary skill in the art will readily appreciate that the method of thepresent disclosure can be implemented using any suitable firstdeflection reference besides a representative onset value taken from asurface electrocardiogram or an intracardiac electrogram.

[0025] In a preferred embodiment, the method of the present disclosurepredicts whether a given stimulation site of a patient will respond toCRT by evaluating the interval from a first deflection to a maximumdeflection of depolarization of a ventricle to receive the CRT therapywhere at least the maximum deflection is detected by an electrode placedat the stimulation site. The first deflection of ventriculardepolarization of the ventricle 108, 112 can be evaluated fromintracardiac or surface electrode signals. An electrogram is generally agraphical depiction of the electrical depolarization or excitement ofthe heart 100 (FIG. 1) that is measured by one or more electrodes placedon or within the heart 100, such as within the right or left ventricles,or alternatively placed on the surface of the patient's body.

[0026] An exemplary pair of electrograms for an intrinsic systolic cycleis shown in FIG. 3 where one electrogram is an intracardiac electrogramand the other is a surface electrogram. Each portion of an electrogramis typically given an alphabetic designation corresponding to apre-determined period of electrical depolarization or excitement. Forexample, the portion of an electrogram that represents atrialdepolarization is commonly referred to as the P-wave (not shown).Similarly, the portion of the electrogram that represents ventriculardepolarization is commonly referred to as the QRS complex comprising aQ-wave, an R-wave, and an S-wave. Moreover, the portion of theelectrogram that represents ventricular recovery or repolarization iscommonly referred to as the T-wave (not shown).

[0027] As shown in FIG. 3, one graph illustrates a maximum deflectionpeak representing the reflexion on the local electrode of the near field(near the electrode) ventricular activation of the left ventriclelabeled LV. Also, shown in FIG. 3 for the intracardiac electrogram isthe first deflection labeled QI corresponding to the onset representingthe reflexion on the local electrode of the start of the far fieldventricular electrical activation. The graph for the surface electrodein FIG. 3 shows the onset of the first deflection of ventriculardepolarization that is labeled Qs. As shown in FIG. 3, the intracardiacgraph, the surface graph for the onset, and the maximum deflection graphare based upon a different time axes so that detail of each of thedifferent waveforms can be appreciated. It should be noted withreference to FIG. 3 that in practice, QI occurs slightly sooner,typically 20 milliseconds sooner, than QS.

[0028] Each period of electrical depolarization or excitementrepresented on the electrogram corresponds to a period of muscularactivation within the heart 100 (FIG. 1). FIGS. 4-6 are schematicillustrations depicting the various periods of muscular activationwithin the heart 100. As shown in FIGS. 4-6, the electrogram data can bemonitored using any suitable electrocardiographic device 150, such as asurface electrocardiograph and/or an implantable heart stimulationdevice (i.e. CRT device) that is connected to leads located on or withinthe heart 100 or through a device that combines information from atleast one intracardiac electrode and at least one surface electrode. Itwill be appreciated by one of ordinary skill in the art that manycombinations of electrodes can be used to derive an electrogram wherethe start of the ventricular activation can be detected as a far fieldsignal.

[0029]FIG. 4 is a schematic illustration showing the period of atrialactivation in response to electrical impulses initiated at thesinoatrial node 120 (corresponding to the P-wave portion as discussedabove). After electrical impulses spread from the sinoatrial node 120,the muscle tissues of the right and left atriums 106, 110 contract topump blood into the right and left ventricles 108, 112, respectively.

[0030]FIG. 5 is a schematic illustration showing the period of aventricular depolarization in response to electrical impulses initiatedat the atrioventricular node 122 that spread through the ventricles 108,112 (corresponding to the QRS portion as discussed above). Afterelectrical impulses spread from the atrioventricular node 122, themuscle tissues of the right and left ventricles 108, 112 contract topump blood to the lungs and throughout the body, respectively.

[0031] In this FIG. 5, a coordinated or synchronous activation of bothventricles and the lateral wall is represented. It is very common inpatients undergoing cardiac resynchronization therapy (CRT) that theseptum and/or the right ventricle activate first with a latelatero-posterior wall activation. Embodiments of the present inventionallows detection with any electrode the low level far field signal thatcorresponds to the start of the ventricular activations, and thencompares the time of occurrence of that signal with the time at whichthe near field activation of the electrode is detected near the site ofstimulation. To be able to resynchronize this site with the earlyactivate site, this site needs to be activated late with respect to thebeginning of the ventricular activation. This allows the comparison ofthis time difference, between the earliest activation and the activationat the stimulation site with a threshold. The comparison provides forthe determination that the site will be a responder site if that time islarger than the therapeutic threshold for CRT to act in a positivemanner.

[0032]FIG. 6 is a schematic illustration showing ventricular recovery orrepolarization (corresponding to the T-wave portion as discussed above).During ventricular repolarization, the membrane potential of the musclecells reverse polarity and return to their resting state, thereby,causing the ventricles to relax in a heart without asynchrony.

[0033] An electrogram of a patient's heart can be used to assess cardiacperformance by validating the existence of cardiac abnormalities, suchas, arrhythmias evinced by an abnormally fast heart rate (e.g.,tachycardia), an abnormally slow heart rate (e.g., bradycardia), or anormal rate but the depolarization is abnormally propagated (e.g.,ectopic, or conduction system defect). The existence of an arrhythmiatypically indicates that the heart's rhythm initiation and/or conductionsystem is functioning abnormally. CRT can be used, among otherapplications, to treat abnormal electrical conduction. In particular,CRT can be used to deliver electrical stimulation to portions of theheart 100 (FIG. 1) to resynchronize the heart's activation, thereby,improving the efficiency of atrial and ventricular contractionsnecessary to circulate blood throughout the body. The amount of benefitderived from CRT, however, typically varies depending upon the severityof the abnormality of the heart's conduction system. Therefore, prior totreating a patient using CRT, it is preferable to evaluate whether theheart's 100 (FIG. 1) conduction system is normal or abnormal.

[0034] This may be done by using the duration of the surface QRS.Patients with a QRS duration of more than 120-130 ms are considered tohave a sufficiently abnormal conduction to benefit from CRT. But once apatient with an abnormal conduction system is found, another problemthat needs to be solved is to determine whether the chosen stimulationsite is good enough to realize the benefits of CRT. For this site to beeffective it needs to be located in a late activate region, henceforthable to resynchronize the ventricles through electrical stimulation.

[0035] To determine if a site is a responder site, both the heart'sventricular conduction system and the chosen site must be assessed.These can be assessed through analysis of the interval (QI-LV or QS-LV)from the first deflection (QI or QS) to the maximum deflection (LV) atthe stimulation site of the ventricular depolarization. Identificationof stimulation sites that may have a positive response to CRT can beperformed using the interval above where at least the maximum deflectionpoint (LV) is measured from an intracardiac electrogram. For example, ifthe interval (QI-LV or QS-LV) is greater than a given threshold, thenthe stimulation site may be considered a responder to CRT, and the CRTdevice for that patient may be configured appropriately.

[0036] Once a stimulation site has been deemed a responder ornon-responder, the CRT device can be configured to stimulate the heartto produce an atrioventricular delay of a duration appropriate for thetype of site as is discussed below. The atrioventricular delay of animplantable device is generally considered to be the length of timebetween an atrial sensed (or stimulated) event and the delivery of aventricular output pulse. For a responder site, the atrioventriculardelay is set to substantially less than the intrinsic, or naturallyoccurring atrioventricular interval, generally to about one-half of theintrinsic interval. This delay may be measured from sensed intrinsicatrial activity to the first ventricular activation in the case of noatrial pacing or may be measured from the atrial pacing spike to thefirst ventricular activation in the case of atrial pacing. For anon-responder site, the atrioventricular delay is set to approximatelythe intrinsic atrioventricular interval, such as 70% of the intrinisicinterval, but at least about 50 milliseconds less than the intrinsicinterval. This setting is somewhat less than the intrinsic interval sothat the intrinsic activity does not occur prior to and interfere withthe stimulation from the device. As discussed for responders above, thisdelay may be measured from the sensed intrinsic atrial activity to thefirst ventricular activation for no atrial pacing or measured from theatrial pacing spike to the first ventricular activation in the case ofatrial pacing. One with ordinary skill in the art will recognize thatother atrioventricular delay settings for responder sites andnon-responder sites are possible as well.

[0037]FIG. 7 shows a graph of the mean percent change in peak rate ofincrease of left ventricle pressure “LV dp/dt” after application of CRTover multiple atrioventricular delays for a group of patients consistingof both responder stimulation sites and non-responder stimulation sites.Responder sites may be defined as those sites where when stimulatedthrough CRT, the patient received an increase in rate of increase ofpeak left ventricle pressure of more than 5%. From the graph, one cansee that a relationship exists between the intrinsic depolarizationinterval (QS-LV) and the increase in peak rate of increase of leftventricle pressure due to CRT. For those stimulation sites having arelatively long first deflection to maximum deflection interval (QS-LV),CRT caused a relatively large increase in peak rate of increase of leftventricle pressure. For those having a relatively short QS-LV interval,CRT caused a relatively small increase or in some instances a decreasein peak rate of increase of left ventricle pressure. The QS-LV data ofFIG. 7 was based on the QS onset value discussed above and that may befound by the process disclosed in commonly owned co-pending U.S. patentapplication Ser. No. 10/004,695 entitled Apparatus and Methods forVentricular Pacing Triggered by Detection of Early VentricularExcitation that applies to an intraventricular unipolar electrogram. Anintraventricular unipolar electrogram is one where the potentialdifference created by the heart's activity is measured from a surfaceelectrode, in our case a patch on the patients chest, to theintraventricular electrode.

[0038] A linear regression of the test cases shows that the correlationof percent change in peak left ventricle pressure to QS-LV is defined bythe equation y=0.2956x−12.371, with a coefficient of determinationR²=0.5289. A threshold of 80 milliseconds appears to be a suitable valuefor distinguishing responder sites from non-responder sites, althoughone skilled in the art will recognize that other threshold values may beapplicable as well. This threshold provides a sensitivity of 81%, whichrepresents the probability of correct classification of stimulationsites as responders, and also provides a specificity of 83%, which isthe probability of correct classification of stimulation sites asnon-responders. Because QT is typically sensed 20 milliseconds earlierthan QS, the threshold of 80 milliseconds for QS-LV may be extended to100 milliseconds for the interval QI-LV, when intracardiac sensing ofthe onset is used.

[0039] One possible embodiment of a CRT system 300 that can be used toimplement the methods for determining whether a stimulation site is aresponder site is illustrated in FIG. 8. As shown in FIG. 8, the CRTsystem 300 generally comprises a programming device 301 that can be usedto program the CRT device and control its diverse parameters (i.e. HR,AV delay, PVARP, etc.). In one possible embodiment, the heart 100 isconnected to various leads 320 having electrodes (not shown) andterminal pins (not shown) that can connect the heart 100 to the CRTsystem 300. The various leads 320 connecting the heart 100 to the CRTsystem 300 will be described in greater detail below.

[0040] The programmer 301 can regulate the stimulation pulses deliveredto the heart 100 using, for example, a telemetry module 302 tocommunicate instructions to an implantable CRT device applying thestimulation pulses. In one possible embodiment, the telemetry module 302is unidirectional (e.g., capable of allowing the programmer 301 toreceive data). However, in an alternative embodiment, the telemetrymodule 302 is bi-directional (e.g., capable of allowing the programmer301 to receive and/or send data). The command input module 304 of animplantable CRT device is configured to interpret the data received fromthe programmer 301 such that the stimulation pulses can be accuratelydistributed according to predetermined criteria, such as, the specificrequirements of the patient being treated.

[0041] A controller 306 of the implantable CRT device can be used tocontrol the specific instructions regarding the stimulation pulsesdelivered to the heart 100. In one possible embodiment, the controller306 can be controlled manually. In an alternative embodiment, however,the controller 306 can be controlled automatically using, for example,feedback received from an intrinsic signal analyzer 338 of theimplantable CRT device. The instructions from the controller 306 arereceived by an electrode switching and output circuitry module 308 ofthe implantable CRT device that delivers the stimulation pulses to theappropriate lead 320 within the heart 100.

[0042] As discussed above, the heart 100 is connected to the CRT system300 using various leads 320. The various leads 320 are preferablyconfigured to carry the CRT stimuli from the implantable CRT device tothe heart 100. Moreover, the various leads 320 can likewise operate in ademand mode, thereby, relaying intrinsic cardiac signals from theheart's I 00 electrical conduction system back to one or more senseamplifiers 310, 312, 314, 316 of the implantable CRT device. In onepossible embodiment, the various leads 320 comprise separate anddistinct leads connecting the CRT system 300 to different portions ofthe heart 100. In particular, the various leads 320 can comprise a lead322 connected to the right-side portion or pump 102 (FIG. 1) of theheart 100, including, for example, a right atrium lead 324 configured tooperate with a right atrium amplifier 310 and a right ventricle lead 326configured to operate with a right ventricle amplifier 312. Similarly,the various leads 320 can comprise a lead 327 connected to the left-sideportion or pump 104 (FIG. 1) of the heart 100, including, for example, afirst left ventricle lead 328 configured to operate with a first leftventricle amplifier 314 and a second left ventricle lead 330 configuredto operate with a second left ventricle amplifier 316.

[0043] As discussed above, the various leads 320 connected to the heart100 can relay intrinsic cardiac signals from the heart's 100 electricalconduction system back to the one or more sense amplifiers 310, 312,314, 316. The intrinsic cardiac signals amplified by the senseamplifiers 310, 312, 314, 316 can then be processed by a signal analyzer338 incorporated in whole or in part by an implantable heart stimulationdevice (i.e., CRT device) receiving the surface electrocardiogram datathrough telemetry 302, or alternatively by the device programmer 301that receives the intracardiac electrogram signal through telemetry 302.One of ordinary skill in the art will appreciate that the signalanalyzer 338 could be either located in the CRT device or in theprogrammer unit or in both depending upon the architectural requirementsof the system and on the degree of autonomy required of the CRT deviceonce disconnected from the programmer. In the embodiment described inFIGS. 8 and 9 the signal analyzer 338 is located in the CRT device.

[0044] Additionally, the CRT system includes an electrocardiographic(ECG) device 343 that includes leads 345 that provide electrodes on thesurface of the patient's body to detect cardiac signals. The cardiacsignals include the ventricular depolarization signal shown in FIG. 3.The ECG device 343 relays this signal to the device programmer 301 forsubsequent relay to the signal processing unit 338 through telemetry anddata input unit 347. Alternatively, the ECG device 343 provides a timingof the first deflection to the programmer 301 rather than relying on theprogrammer 301 or signal analyzer 338 to determine from the cardiacsignal when the first deflection occurred. The electrocardiograph is aset of amplifiers and switches with connectors for the electrodeslocated in the surface of the body of the patient, and this set ofcomponents could be integrated into the programmer and be anindistinguishable part of the programmer system.

[0045] The intrinsic signal analyzer 338 generally can comprise adetection module 340 that is configured to analyze the intracardiacelectrogram and/or surface electrocardiogram information to detect thefirst deflection (QS) and maximum deflection of local ventriculardepolarization (LV) values discussed above with reference to FIG. 3. Inthe embodiment described by FIG. 8 the detection module 340 is equippedto analyze the surface electrocardiogram information or to receive theQS times directly from the programmer or electrocardiographic unit. TheQS and LV values are then processed by the processing module 342 todetect a responder or non-responder site and the result is implementedby the configuration module 344 by setting the atrioventricular delay asappropriate for the particular type of site by interacting with thecontroller 306. The processing performed by processing module 342 isdiscussed in more detail below with reference to FIG. 10.

[0046] Another possible embodiment of a CRT system 300 that can be usedto implement the methods for determining whether a patient is aresponder is illustrated in FIG. 9 and comprises many of the samecomponents as the embodiment of FIG. 8 which function in the same manneras previously discussed, except that no surface electrocardiographicdevice is utilized in the embodiment of FIG. 9.

[0047] As discussed above, the various leads 320 connected to the heart100 can relay intrinsic cardiac signals from the heart's 100 electricalconduction system back to the one or more sense amplifiers 310, 312,314, 316. The intrinsic cardiac signals amplified by the senseamplifiers 310, 312, 314, 316 can then be processed by an intrinsicsignal analyzer 338 incorporated in whole or in part by the implantableheart stimulation device (i.e., CRT device) or a device programmer 201that receives intracardiac signals from the implantable CRT devicethrough data input/output module 349 and telemetry 302. The intrinsicsignal analyzer 338 generally can comprise a detection module 340 thatis configured to analyze the intracardiac electrogram information todetect both the first deflection (QI) and the maximum deflection (LV) ofventricular depolarization. The QI-LV values are then processed by theprocessing module 342 as discussed below with reference to FIG. 10, andthe result is implemented by the configuration module 344 setting theappropriate atrioventricular delay.

[0048] The method of the present disclosure can be implemented using aCRT system as shown in FIG. 8 or 9 comprising various devices and/orprogrammers, including implantable or external CRT devices and/orprogrammers such as a CRT tachy or brady system. Accordingly, the methodof the present disclosure can be implemented as logical operationscontrolling a suitable CRT device and/or programmer. The logicaloperations of the present disclosure can be implemented: (1) as asequence of computer implemented steps running on the CRT device and/orprogrammer; and (2) as interconnected machine modules within the CRTdevice and/or programmer.

[0049] The implementation is a matter of choice dependant on theperformance requirements of the CRT device and/or programmerimplementing the method of the present disclosure and the componentsselected by or utilized by the users of the method. Accordingly, thelogical operations making up the embodiments of the method of thepresent disclosure described herein can be referred to variously asoperations, steps, or modules. It will be recognized by one of ordinaryskill in the art that the operations, steps, and modules may beimplemented in software, in firmware, in special purpose digital logic,analog circuits, and any combination thereof without deviating from thespirit and scope of the present invention as recited within the claimsattached hereto.

[0050]FIG. 10 shows an exemplary embodiment 346 of the logicaloperations of the processing module 342. The process begins by theprocessing module 342 receiving the QI or QS and LV time values from thesignals measured by detection module 340 and/or ECG device 343 atreceive operation 348. At interval operation 350, the processing module342 computes the time interval between the QI or QS and LV values. Atquery operation 352, the processing module 342 compares the QI-LV orQS-LV interval to the threshold, such as 100 milliseconds for QI-LV and80 milliseconds for QS-LV.

[0051] If the processing module 342 determines that QI-LV or QS-LV isgreater than the threshold, then the processing module 342 selects anatrioventricular delay that is about one-half of the intrinsicatrioventricular delay at delay operation 354. If the processing module342 determines that QI-LV or QS-LV is less than or equal to thethreshold, then the processing module 342 selects an atrioventriculardelay that is approximately equal to the intrinsic atrioventriculardelay at delay operation 356. As discussed above, it is desirable atdelay operation 356 to set the atrioventricular delay to the intrinsicatrioventricular delay value less a small delay factor such that theatrioventricular delay is around 70% of the intrinsic interval but isalways at least 50 milliseconds less than the intrinsic interval. Theconfiguration module 344 then implements the atrioventricular delayselected by processing module 342 when applying CRT or other pacingtherapy to the patient.

[0052] While the invention has been particularly shown and describedwith reference to preferred embodiments thereof, it will be understoodby those skilled in the art that various other changes in the form anddetails may be made therein without departing from the spirit and scopeof the invention.

What is claimed is:
 1. A method for predicting acute response to cardiacresynchronization therapy at a stimulation site of a patient, comprisingthe steps of: inserting a lead to the heart of the patient such that anelectrode of the lead is positioned at the stimulation site; detecting afirst deflection of an intrinsic ventricular depolarization; detecting amaximum deflection of the intrinsic ventricular depolarization at theelectrode; and comparing an interval of time between the firstdeflection and the maximum deflection to a threshold to determinewhether the stimulation site is a responder site.
 2. The method of claim1, wherein the lead is electrically connected to an implantable devicethat delivers cardiac resynchronization therapy, and wherein the methodfurther comprises the step of setting the atrioventricular delay of theimplantable device to substantially less than an intrinsicatrioventricular delay of the patient when the stimulation site is aresponder site.
 3. The method of claim 2, wherein the method furthercomprises the step of setting the atrioventricular delay of theimplantable device to approximately the intrinsic atrioventricular delayof the patient when the stimulation site is a non-responder site.
 4. Themethod of claim 1, wherein detecting the first deflection comprisesdetecting the onset of the first deflection detected at the electrode ofthe lead.
 5. The method of claim 1, wherein the step of measuring thefirst deflection of ventricular depolarization comprises measuring theonset of the first deflection detected at the electrode of the lead. 6.The method of claim 5, wherein the threshold is 100 milliseconds.
 7. Themethod of claim 1, wherein the step of measuring the first deflection ofventricular depolarization comprises measuring an onset of the firstdeflection detected by a surface electrocardiogram.
 8. The method ofclaim 7, wherein the threshold is 80 milliseconds.
 9. A system forpredicting acute response to cardiac resynchronization therapy at astimulation site of a patient, comprising: a lead having an electrodeplaced at the stimulation site that detects an intrinsic ventriculardepolarization; a surface electrocardiograph machine that detects theintrinsic ventricular depolarization; a processing device that finds aninterval of time between a first deflection of the intrinsic ventriculardepolarization as detected by the surface electrocardiograph machine anda maximum deflection of the intrinsic ventricular depolarization asdetected by the electrode of the lead, and compares the interval to athreshold to determine whether the stimulation site is a responder. 10.The system of claim 9, wherein the processing device is furtherconfigured to communicate with an implantable device of the patient toset the atrioventricular delay of the implantable device tosubstantially less than an intrinsic atrioventricular delay of thepatient when the interval is greater than the threshold.
 11. The systemof claim 10, wherein the processing device is further configured tocommunicate with the implantable device to set the atrioventriculardelay of the implantable device to approximately the intrinsicatrioventricular delay when the interval is less than the threshold. 12.The system of claim 9, wherein the threshold is 80 milliseconds.
 13. Asystem for predicting acute response to cardiac resynchronizationtherapy at a stimulation site of a patient, comprising: a lead having anelectrode placed at the stimulation site that detects an intrinsicventricular depolarization; a processing device that finds an intervalof time between a first deflection and a maximum deflection of theintrinsic ventricular depolarization as detected by the electrode andcompares the interval to a threshold to determine whether thestimulation site is a responder.
 14. The system of claim 13, wherein theprocessing device is further configured to communicate with animplantable device to set the atrioventricular delay of the implantabledevice to substantially less than an intrinsic atrioventricular delay ofthe patient when the interval is greater than the threshold.
 15. Thesystem of claim 13, wherein the processing device is further configuredto communicate with an implantable device to set the atrioventriculardelay of the implantable device to approximately an intrinsicatrioventricular delay when the interval is less than the threshold. 16.The system of claim 13, wherein the processing device is included in animplantable device of the patient that is connected to the lead andwherein the processing device sets the atrioventricular delay of theimplantable device to substantially less than an intrinsicatrioventricular delay of the patient when the interval is greater thanthe threshold.
 17. The system of claim 13, wherein the processing deviceis included in an implantable device of the patient that is connected tothe lead and wherein the processing device sets the atrioventriculardelay of the implantable device to approximately an intrinsicatrioventricular delay of the patient when the interval is less than thethreshold.
 18. The system of claim 13, wherein the threshold is 80milliseconds.
 19. A system for predicting acute response to cardiacresynchronization therapy at a stimulation site of a patient,comprising: sensing means for detecting an intrinsic ventriculardepolarization wherein the sensing means comprises at least an electrodepositioned at the stimulation site; timing means for detecting aninterval of time between a first deflection and a maximum deflection ofthe intrinsic ventricular depolarization; and comparison means forcomparing the interval of time between the first deflection and themaximum deflection to a threshold to determine whether the stimulationsite is a responder.
 20. The system of claim 19, wherein the sensingmeans further comprises a surface sensing means to detect the intrinsicventricular depolarization, and wherein the timing means detects theinterval by obtaining the first deflection from the surface sensingmeans.
 21. The system of claim 19, wherein the timing means detects theinterval by obtaining the first deflection from the electrode positionedat the stimulation site.
 22. The system of claim 19, further comprisingstimulation means for providing resynchronization therapy at thestimulation site and wherein the stimulation means provides anatrioventricular delay substantially less than an intrinsicatrioventricular delay of the patient when the stimulation site is aresponder site.
 23. The system of claim 19, further comprisingstimulation means for providing resynchronization therapy at thestimulation site and wherein the stimulation means provides anatrioventricular delay approximately equal to the intrinsicatrioventricular delay of the patient when the stimulation site is anon-responder site.